Epigenetic mechanisms regulate stage differentiation in the minimized protozoan Giardia lamblia
Epigenetic mechanisms regulate stage differentiation in the minimized protozoan Giardia lamblia
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DOI：
10.1111/j.1365-2958.2010.07062.x
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发表时间：
2010-04-01
影响因子：
3.6
通讯作者：
Hehl, Adrian B.
中科院分区：
文献类型：
--
作者：
Sonda, Sabrina;Morf, Laura;Hehl, Adrian B.
组蛋白修饰是发育过程中调控基因表达和细胞表型建立与维持的重要机制。通过组蛋白乙酰化酶和去乙酰化酶（HDAC）调节组蛋白乙酰化似乎在确定基因表达模式中特别重要。在这项研究中，我们探讨了HDAC抑制对人类病原体贾第鞭毛虫，高度减少的寄生原生动物，其特征在于最小化的细胞过程的生命周期的影响。我们发现HDAC抑制剂FR 235222增加了组蛋白乙酰化的水平，并诱导了增殖和包囊寄生虫中约2%的基因的转录调节。此外，我们的分析表明，组蛋白乙酰化水平下降，在分化成囊肿，感染阶段的寄生虫。重要的是，在包囊形成期间，FR 235222处理逆转了这种组蛋白低乙酰化，并有效地阻断了包囊的形成。这些结果提供了第一个直接的证据，在这个简单的真核生物的基因表达的表观遗传调控。这表明，组蛋白乙酰化的调节参与控制贾第鞭毛虫阶段分化，并确定表观遗传机制作为一个有前途的目标，以防止贾第鞭毛虫传播。
P>Histone modification is an important mechanism regulating both gene expression and the establishment and maintenance of cellular phenotypes during development. Regulation of histone acetylation via histone acetylases and deacetylases (HDACs) appears to be particularly crucial in determining gene expression patterns. In this study we explored the effect of HDAC inhibition on the life cycle of the human pathogen Giardia lamblia, a highly reduced parasitic protozoan characterized by minimized cellular processes. We found that the HDAC inhibitor FR235222 increased the level of histone acetylation and induced transcriptional regulation of similar to 2% of genes in proliferating and encysting parasites. In addition, our analyses showed that the levels of histone acetylation decreased during differentiation into cysts, the infective stage of the parasite. Importantly, FR235222 treatment during encystation reversed this histone hypo-acetylation and potently blocked the formation of cysts. These results provide the first direct evidence for epigenetic regulation of gene expression in this simple eukaryote. This suggests that regulation of histone acetylation is involved in the control of Giardia stage differentiation, and identifies epigenetic mechanisms as a promising target to prevent Giardia transmission.